Oxidative stress and inflammation have been proposed to play key roles in aging and[unreadable] neurodegenerative diseases associated with aging such Alzheimer's disease and Parkinson's disease.[unreadable] Thus, an understanding of the mechanisms in the brain that leads to an increase in inflammation and[unreadable] oxidative stress could lead to rational therapeutic interventions in aging and neurodegenerative diseases.[unreadable] We have been examining nutritional interventions such as spinach or blueberries, which lead to[unreadable] improvements in learning and memory in aged rats and modulation of many biomarkers of brain aging. In[unreadable] the past granting period, we have demonstrated that inflammation and oxidative stress occur in the aged[unreadable] brain and that these processes may contribute to the declines in cognitive function. We have[unreadable] demonstrated that both natural and pharmaceutical antioxidant and anti-inflammatory agents are capable[unreadable] of improving cognitive deficits in aged rats and this is concomitant with changes in neuronal signal[unreadable] transduction. We will examine potential mechanisms by which these diets alter brain aging. One potential[unreadable] mechanism is an amelioration of an increase in inflammation with age. Microglial cells are an important[unreadable] source of reactive oxygen species (ROS) in the brain as well as other inflammatory signals such as proinflammatory[unreadable] cytokines and therefore may play a central role in modulating CNS oxidative stress and[unreadable] neurodegenerative diseases. We plan to investigate immune function in the progression of[unreadable] neurodegeneration in the aged brain and the potential for therapeutic intervention in neurodegenerative[unreadable] diseases such as Alzheimer's disease. We hypothesize that oxidative stress and inflammation are[unreadable] primary drivers of neuronal dysfunction in the aged brain; furthermore, age-related changes in microglia[unreadable] are the critical primary events in brain aging and neurodegenerative disease. Specifically, in the[unreadable] cerebellum, microglial production of tumor necrosis factor (TNF)alpha leads to further inflammation and[unreadable] oxidative stress. Therapeutic interventions that reduce TNFalpha and/or microglial activation will[unreadable] improve neuronal function and concomitantly learning and memory in aged animals will be[unreadable] improved.